PXD037068

PXD037068 is an original dataset announced via ProteomeXchange.

Title	SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis
Description	The coronavirus disease 2019 (COVID-19) pandemic has devastated global health. Identifying key host factors essential for SARS-CoV-2 RNA replication is expected to unravel cellular targets for the development of broad-spectrum antiviral drugs which have been quested for the preparedness of future viral outbreaks. Here, we have identified host proteins that associate with non-structural protein 12 (nsp12), the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 using a mass spectrometry (MS)-based proteomic approach. Among the candidate factors, CDK2 (Cyclin-dependent kinase 2), a member of cyclin-dependent kinases, interacts with nsp12 and causes its phosphorylation at T20, thus facilitating the assembly of the RdRp complex consisting of nsp12, nsp7 and nsp8 and promoting efficient synthesis of viral RNA. The crucial role of CDK2 in viral RdRp function is further supported by our observation that CDK2 inhibitors potently impair viral RNA synthesis and SARS-CoV-2 infection. Taken together, we have discovered CDK2 as a key host factor of SARS-CoV-2 RdRp complex, thus serving a promising target for the development of SARS-CoV-2 RdRp inhibitors.
HostingRepository	iProX
AnnounceDate	2022-09-28
AnnouncementXML	Submission_2023-03-28_20:34:29.602.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Saisai Guo
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive Plus; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-28 19:25:13	ID requested
1	2023-03-27 19:42:35	announced
⏵ 2	2023-03-28 20:34:30	announced	2023-03-29: Update publication information.

Guo S, Lei X, Chang Y, Zhao J, Wang J, Dong X, Liu Q, Zhang Z, Wang L, Yi D, Ma L, Li Q, Zhang Y, Ding J, Liang C, Li X, Guo F, Wang J, Cen S, SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis. Signal Transduct Target Ther, 7(1):400(2022) [pubmed]

submitter keyword: SARS-CoV-2, RdRp, CDK, phosphorylation, nsp12

Shan Cen
contact affiliation	Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School
contact email	shancen@imb.pumc.edu.cn
lab head
Saisai Guo
contact affiliation	Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School
contact email	gss2029@163.com
dataset submitter

iProX dataset URI